Fluorescent semiconductor quantum dots (QDs) have generated wide interest since their initial development and hold exciting potential for molecular imaging in living biological samples. Much of the excitement towards QDs arises from their unique optical properties as fluorescence imaging probes, as compared to traditional organic fluorophores, such as high quantum yield, high molar extinction coefficients, narrow emission spectra, size-dependent tunable emission, and high photostability, all of which make QDs appealing for imaging living subjects. QDs fabricated with various coating molecules and functionalized with biomolecules such as small peptides, proteins, antibodies, and nucleic acids, have been employed in a number of imaging studies. All reported QDs, however, need excitation from external illumination sources in order to fluoresce, which often presents an inherent challenge in imaging opaque subjects such as small living animals. In biological tissues, there are ubiquitous, endogenous chromophores such as collagens, porphyrins, and flavins, which are also excited by the illumination source and lead to significant background autofluorescence. In addition, short-wavelength excitation photons are largely scattered and absorbed in tissues, therefore, little light reaches and excites QDs present at non-superficial locations.